Burn injury, one of the most common diseases in primary care, is also a major cause of death and disability. The aim of this study was to evaluate the effect of Propolis in thermal burn wounds in guinea pigs and to compare its effects with those of silver sulfadiazine (SSD), the most widely used burn treatment. Burn injury was produced in guinea pigs by immersion of the shaved dorsal area to hot water. Male Guinea pigs of approximate (550 g body weight each) were divided into five groups. In the normal group; Guinea pigs were orally administered with 0.9% isotonic saline solution at a dose (10 ml/kg body weight). The second, served as positive control group which were orally administered with 0.9% isotonic saline solution at a dose (10 ml/kg body weight), then standard burns were obtained on the dorsal skin. The 3^rd  group  was treated by Propolis topically (100 mg/kg b.wt), the 4^th group treated with silver sulfadiazine topically (layer thickness of about 3–5 mm) and the 5^th group treated with Propolis orally and  topically (100 mg/kg b.wt). Every group contains 20 animals and sacrificed at 15 and 30 days post-treatment by Propolis or SSD (10 animals per each). The results are recorded after monitoring the CBC including (RBCs, WBCs, platelets, Hb content and HCT percentage), lipid profile including (total cholesterol (TC), triglyceride (TGs), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (vLDL)) and the skin antioxidant status (catalase activity (CAT),  superoxide dismutase (SOD) and serum nitric oxide (NO) beside malondialdehyde (MDA) concentration) were also monitored during the study compared to normal animals. The recorded results declared that, the treatment with Propolis has shown an ameliorative effect on burn healing. These observations and investigations were the pacemaker for the hypothesized ameliorating activity of Propolis in the present study.