The present study was carried out in Rabbit Research Unit at Sakha Research Station located in Kafr El-Shiekh governorate, Egypt to assess the impact of N-acetylecysteine (NAC) administration on the physiological, reproductive and productive performance of rabbit does. A total number of 21 pregnant, healthy, primiparous New Zealand White (NZW) rabbit does aged between 5-6 months with an average initial body weight (BW) of 3052 g were used. They were divided into three equal groups. The first group (G1) was served as control group without any administration. The second and third groups (G2 and G3) were injected subcutaneously with 50 and 100 mg NAC / kg BW, respectively. The injection with NAC doses started on day 14 of pregnancy and continued for seven consecutive days. The experiment lasted continuously for three months. The obtained results showed that, NAC treatment reduced the oxidative stress in pregnant rabbit does, G2 and G3 had the highest values of GST and the lowest values of both MDA and H 2 O 2 in comparison with those of G1.Total protein, albumin, globulin and A/G ratio did not significantly affected by NAC injection and tended to increase with pregnancy progress. In contrast, level of triglycerides decreased (P<0.05) in G2 and G3 than that of G1 and declined with progress of gestation till kindling. Treated groups decreased their blood urea nitrogen (BUN) values and increased their creatinine (CR) levels than those of G1. With progress of pregnancy, levels of BUN tended to decrease and CR levels tented to increase. Both transaminase enzymes (AST and ALT) activities decreased by NAC treatment and by pregnancy progress, particularly in G3. The changes in live BW of does in the three groups across the experimental period were insignificant. NAC injection achieved weaning day, G2 and G3 had heavier kits' weight than those in G1 by 26 and 20 %, respectively. Litter size increased obviously due to NAC treatment by 19 to 35 % in G2 and by 5.5 to 23.1 % in G3 than that in G1 during the all experimental days. Mortality rate reduced by NAC injection being the lowest in G2 (4.7 %) followed by G3 (11.2%) and the highest in G1 (23.6 %). Total milk yield was increased significantly in G3 and insignificantly in G2 compared to that of G1 by 17.5 and 4.5 %,respectively. The high dose was more effective in promoting milk production. The effect of NAC treatment on all milk components was insignificant, except milk lactose. From the first wk to the last wk, milk composition (%) of milk protein, milk lactose, milk total solids and milk solids not fats increased (P<0.05) whereas milk fat decreased. In conclusion, this study proved not only the effectiveness, but also the safety of NAC application and its capability to improve rabbit's performance particularly with high dose (100 mg/kg BW). Further studies are urgently needed to confirm our findings.