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Objectives: Our study reports the immunomodulatory potency of Quercus infectoria gall extract in vitro . The aqueous extract was prepared and examined for its effects on cell proliferation, phagocytic activity, nitric oxide (NO) production, and cytokine synthesis by murine macrophages., Methods: Proliferative, phagocytic activity, and NO production of extract-treated and control cells were studied using proliferative assay, flow cytometry, and Griess reaction, respectively. An enzyme-linked immunosorbent assay was performed to determine the levels of pro- and anti-inflammatory cytokines in the macrophage culture., Results: Treated macrophages had a higher proliferative rate and phagocytic activity compared to untreated macrophages. The cell treatment with an extract concentration of 64 μg/mL demonstrated a significant decrease in NO production ( p < 0.001). An increase in cytokine levels (IL-2, IL-5, IL-10, IL-17A, IL-23, TGF-β1) was observed; however, this increase was not statistically significant., Conclusions: Our study suggests that gall extract possesses the potential for augmenting immunomodulatory activity by cellular mediated mechanism and could play a role in regulating the innate immune response., (The OMJ is Published Bimonthly and Copyrighted 2021 by the OMSB.)