The main aim of this study is to assess the effects of grape seed extract (GSE) on immune performance and, antioxidant capacity in rabbit does exposed to heat stress in Sakha Animal Research Station, Kafr El-Sheikh governorate, Egypt. Twenty-four healthy mature females of APRI bred were randomly allocated into 3 groups (eight rabbit does each). The first group (GI), received a regular rabbit diet and was maintained as a control group. Rabbits from the second group (G2) were treated with GSE by oral gavage at the dose of 125 mg/kg body weight. The third group (G3) of rabbits was treated with GSE by oral gavage at a dose of 250 mg/kg body weight. Rabbits were kept in cages under a constant temperature of 28-30Cº and 12:12 hour “light: dark cycle". Food and water were provided adlibitum. The lipid parameters, Cholesterol, Triglycerides, and High-Density Lipoprotein and Low-Density Lipoprotein were determined. For biochemical and histopathological examinations specimens from liver, kidney, and ovary tissue were collected. The obtained results from in vitro data demonstrated that GSE (125-250 mg/kg) treatments increased immunosystem and decreased oxidative stress, and also suggested that GSE plays a beneficial role in the enhancement of liver and kidney function and improves the ovarian activity.