An experimental study was conducted to examine the effects of adding serine-protease from Bacillus licheniformis on performance and physiological parameters of broiler chickens under Egyptian condition. A total of 600 one-day-old chicks were randomly divided into four experimental treatments. The treatments consisted of the control diet with 0, 100, 200 and 300 mg/kg serine-protease. Protease supplementation increased (P < 0.05) body weights (BW). Feed conversion ratio (FCR) was improved (P < 0.05) due to 200 and 300 mg/kg protease supplementation. The dry matter and crude protein digestibilities were enhanced (P < 0.05) by both 200 and 300 mg/kg protease supplementation. Plasma albumin and high-density lipoprotein (HDL) concentrations were increased (P < 0.05), while plasma total cholesterol (CHO) and low-density lipoprotein (LDL) concentrations were decreased (P < 0.05) at 100, 200, and 300 mg/kg of protease. Liver malondialdehyde (MDA) levels were declined (P < 0.05) due to 200 and 300 mg /kg protease supplementation. Supplementing 100, 200, and 300 mg/kg of protease increased (P < 0.05) lysine, methionine, and threonine levels in breast muscle. In conclusion, exogenous serine-protease could be used as a feed additive in broiler nutrition and supplementing 200∼300 mg/kg was sufficient to improve growth performance, probably because of its mechanism to enhance protein digestibility.