BACKGROUND The objective was to observe the effect of oral anti-CD3 monoclonal antibody (mAb) on non-obese diabetic mice, pregnancy, and offspring. METHODS Three protocols are classified as: (1) Twenty non-obese diabetic/ShiLtJ female mice were monitored for type 1 diabetes mellitus. If the blood glucose level was ≥ 250 mg/dL, the mice were treated for 8 days with either 50 or 100 µg oral anti-CD3 monoclonal antibody. If the diabetes resolved, the mice were bred. (2) F1 offspring were monitored for diabetes; 15 female mice became diabetic. Non-diabetic F1 female mice were divided into two groups [ten antibody (Ab) and ten control (C)] and bred. Ab female mice were given 100 µg monoclonal antibody before diabetes development and during pregnancy for 6 weeks. (3) Twenty-five F2 Ab and 23 F2 C mice were monitored. At 15-17 weeks, Ab mice, both female and male, were given 100 µg monoclonal antibody for 8 weeks. RESULTS (1) The diabetes in four female mice treated with 50 µg did not resolve; in three of the six diabetic female mice treated with 100 µg, the diabetes resolved and the mice were bred. The remaining ten non-diabetic female mice were given 100 µg oral monoclonal antibody and then bred. No diabetes developed during pregnancy; 13 litters were born. (2) Three diabetic Ab female mice sustained their pregnancies versus one diabetic C female mouse (p ≤ 0.05). (3) At 30 weeks, six Ab female and three Ab male mice and seven C female and three C male mice developed diabetes. The number of diabetic Ab and C mice was not different; diagnosis age was significantly different-Ab 23.3 ± 5.1 and C 18.8 ± 3.7 weeks (p ≤ 0.05). CONCLUSIONS In female non-obese diabetic mice, oral anti-CD3 monoclonal antibody was effective in reversing diabetes and allowing pregnancy and extending longevity, but it did not prevent diabetes in the offspring.