This is a randomized, 2-part, 2-arm, open-label, parallel-group, multi-center study to compare the PK of etrolizumab administered subcutaneously by an AI (test device) or a PFS-NSD (reference device) in healthy participants. The study will comprise a pilot cohort (Part 1) to estimate the geometric mean ratio (GMR) and variability of the maximum observed concentration (Cmax) and area under the concentration-time curve (AUC) to confirm or determine the sample size for the pivotal cohort (Part 2). The pivotal cohort will demonstrate exposure comparability of Cmax, AUC from Hour 0 to the last measurable concentration (AUClast), and AUC from Hour 0 to extrapolated infinite time (AUC0-inf), values for a single dose of etrolizumab administered subcutaneously either by the AI or the PFS-NSD.

Inclusion Criteria:

• Within the body weight range of 60 to 100 kilograms, inclusive (for the pivotal cohort [Part 2] only)
• Within body mass index (BMI) range 18.0 to 30.0 kilograms per square meter (kg/m^2), inclusive
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs
• Females will be non-pregnant, non-lactating, and either postmenopausal (at least 12 months of non-therapy-induced amenorrhea)/surgically sterile (e.g., tubal ligation, hysterectomy) for at least 90 days prior to enrolment, or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration
• Males will either be sterile or agree to remain abstinent/use a highly effective method of contraception for at least 24 weeks after study drug administration. Male participants will refrain from sperm donation from Check-in (Day -1) until 24 weeks following study drug administration

Exclusion Criteria:

• Any prior treatment with etrolizumab or other anti-integrin agents (including natalizumab, vedolizumab, and efalizumab)
• Any prior treatment with anti-mucosal addressin cell adhesion molecule 1 (anti-MAdCAM-1) agents
• Any prior treatment with rituximab
• Received intravenous corticosteroids within 30 days prior to Screening
• Use of agents that deplete B or T cells (e.g., alemtuzumab, rituximab, or visilizumab) within 12 months prior to randomization
• Any prior immunosuppressive agents (including cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil)
• Chronic nonsteroidal anti-inflammatory drug (NSAID) use
• Use of any prescription medications/products within 14 days prior to Check in (Day -1)
• History of demyelinating disease
• Neurological conditions or diseases
• History of cancer
• History of alcoholism or drug addiction within less than (<) 1 year prior to Screening
• History of active or latent tuberculosis (TB), regardless of treatment history
• History of recurrent opportunistic infections and/or history of severe disseminated viral infections
• Positive for human immunodeficiency virus (HIV) antibody
• Any current or recent signs or symptoms of infection
• Pregnant or lactating
• Hospitalized within 4 weeks prior to and during Screening
• History of organ transplant
• Presence of skin rash at Screening or history of other skin disorders
• Tattoos, scars, chronic rashes, or sunburn in the area of the designated injection site