Abstract: Inflammation is a complex biological response to harmful stimuli such as infection, injury, and irritants, often associated with tissue damage and metabolic disturbances when excessive or prolonged. The present study was designed to evaluate the effects of Cayenne pepper (Capsicum annuum) extract on experimentally induced acute inflammation in rats. The anti-inflammatory potential was assessed using carrageenan-, histamine-, and dextran-induced rat paw edema models. Rats were divided into five groups: normal control, inflammation control, Cayenne pepper extract-treated groups (200 mg/kg and 400 mg/kg, p.o.), and a standard group treated with diclofenac sodium (10 mg/kg, p.o.). Paw volume was measured at different time intervals, and serum biochemical parameters including total protein, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed to assess systemic effects. The results showed that Carrageenan, histamine, and dextran administration produced a significant increase in paw edema compared to the normal control group. Treatment with Cayenne pepper extract significantly reduced paw swelling in a dose-dependent manner, with the higher dose showing greater efficacy and comparable effects to diclofenac sodium. Biochemical analysis revealed that inflammation caused a significant decrease in total protein and albumin levels, along with elevated ALP, AST, and ALT activities. Treatment with the extract significantly restored these parameters toward normal values, indicating protection against tissue injury and metabolic imbalance. The observed effects may be attributed to bioactive constituents such as capsaicin, flavonoids, and phenolic compounds present in the extract. In conclusion, Cayenne pepper (Capsicum annuum) extract demonstrated significant protective effects against experimentally induced inflammation and associated biochemical alterations in rats. These findings suggest its potential as a natural agent for managing inflammatory conditions, warranting further investigation into its active components and mechanisms of action.