The investigators propose a pilot, single blind, placebo run-in, dose finding study of pioglitazone in children with autism with the ultimate goal of identifying appropriate dosing and outcome measures for a larger follow-up randomized placebo controlled clinical trial. The specific aims of this study are: 1) To examine the safety of pioglitazone in children with autism spectrum disorders (ASD) ages 5-12 years; 2) To identify appropriate outcome measures to be used in a follow-up multisite randomized control trial of pioglitazone in children with ASD; 3) To determine the maximum tolerated dose to be used in the follow-up multisite randomized controlled trial; 4) To examine the effect of pioglitazone on markers of inflammation (cytokine levels) and oxidative stress (superoxide dismutase, malonyl aldehydes); 5) To explore the relationship between different doses and response to treatment.

Inclusion Criteria:

1. Male or female outpatients 5-12 years of age inclusive (see Note below).
2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV) criteria. DSM-IV criteria for Autistic Disorder or Asperger's Disorder (autism spectrum disorder) will be confirmed by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM-IV criteria, the Autism Diagnostic Observation Schedule (ADOS-G) and the Autism Diagnostic Interview-Revised (ADI-R).
3. Have a Clinical Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Baseline.
4. If already receiving stable non-pharmacologic educational, behavioural, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study.
5. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age.
2. Families without sufficient command of the English Language.
3. Patients with any primary psychiatric diagnosis other than autism at Screening.
4. Patients with a current neurological disease, including, but not limited to, movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes.
5. Pregnant female patients, female patients who are sexually active, female patients using the birth control pill for whatever reason.
6. Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. Patients with stable epilepsy (no seizures for 6 months) and on stable doses of antiepileptic medications (no changes in 3 months) will be allowed in the study.
7. Patients taking psychoactive medication(s).
8. Patients taking insulin.
9. Patients unable to tolerate venipuncture procedures for blood sampling.
10. Patients with parent(s)/caregiver(s) who smoke.
11. Patients who have had previous bladder infection(s).
12. Patients with a family history of bladder cancer.