This study investigated the effects of oral administration of β-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of β-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between β-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of β-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with β-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by β-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of β-glucan was significantly upregulated and enhanced the immune response. β-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 β-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of β-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.