This present study investigates the effect of an aqueous seed extract of Aframomum melegueta, on leukocytes migration and on phenylhydrazine-treated rat red blood cells (RBC). The effect of Aframomum melegueta on the number of white blood cells (WBC), in inflammatory exudates, was assessed by utilizing the granuloma air pouch model, for chronic inflammation in carrageenin-treated rats. The extract was tested for its anti-oxidant and membrane-stabilizing effects, in rat RBC exposed to phenylhydrazine. Aframomum melegueta was found to significantly reduce the number of WBC, in the fluid in a dose-related manner. The extract also produced significant inhibition of rat red blood cells lysis exposed to phenylhydrazine, which suggests a membrane-stabilizing effect. It further demonstrated a potent anti-oxidant activity, as it significantly reduced the levels of malonydialdehyde (MDA) formation in rat RBC exposed to phenylhydrazine. The results of this study, suggest that Aframomum melegueta possess membrane-stabilizing activity, along with anti-oxidant property and may also have a modifying effect, on the responses of WBC to tissue injury.