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The goal of this study was to look into the immunomodulatory activity of aqueous extract of Pisonia alba root (PARE) with a focus on splenocyte proliferation and cytokine production. After immunisation with Salmonella antigen, antibody titers were determined by tube agglutination and indirect ELISA assay in four groups of mice: control, antigen alone, and PARE-treated (400 and 800 mg/kg for 21 days), while cellular immunity was studied in three groups of rats (control and PARE-treated - 400 and 800 mg/kg for 21 days). Concanavalin-A (Con-A) was used to stimulate splenocytes from untreated and PARE-treated rats, and the optical density (OD) and stimulation index were measured. To test the effect on splenocyte proliferation, control rats' splenocytes were treated in vitro with PARE (50–1600 g/ml) and Con-A. ELISA kits were used to measure interleukin-2 (IL-2) and IL-6 levels in splenocyte supernatants from control and PARE-treated rats, as well as after in vitro treatment of splenocytes with PARE (50–1600 g/ml). Both approaches revealed a considerable rise in antibody titer in PARE-treated mice and a significant increase in skin thickness in rats after DNCB challenge, indicating that PARE has humoral and cell-mediated immunostimulant potential. After ex vivo and in vitro exposure of splenocytes to PARE and sensitization with Con-A, large increases in OD and stimulation index were found, as well as significant elevations in IL-2 and IL-6 levels in splenocytes supernantant. PARE's humoral and cell-mediated immunostimulant effect appears to be mediated by splenocyte proliferation and enhanced cytokine production, particularly IL-2 and IL-6.