In this study, the impact and underlying mechanisms of zinc (Zn) on the immune function of the head kidney, spleen and skin of grass carp were investigated. A 60-day growth test was first conducted by feeding diets containing seven different Zn levels, Zn lactate (10.71, 30.21, 49.84, 72.31, 92.56 and 110.78 mg Zn/kg diet) and Zn sulfate (56.9 mg Zn/kg diet); after that, selected test fish were subjected to 14-day Aeromonas hydrophila. The findings indicated that, in comparison to the group with Zn deficiency, (1) the optimal Zn level decreased parenchymal cell lysis and necrosis, cellular vacuolar degeneration and iron-containing haemoflavin in head kidney and spleen; (2) the optimal Zn level significantly increased the levels of lysozyme, complement proteins C3 and C4, immunoglobulin IgM, and the transcript levels of antimicrobial peptides in head kidney, spleen and skin; (3) the optimal Zn level demonstrated a mitigating effect on inflammatory responses, partially attributed to the downregulation of pro-inflammatory cytokines mRNA levels and the upregulation of anti-inflammatory cytokines mRNA levels in head kidney, spleen and skin. These effects may partially mediated by the signaling pathways [IKKα, β, γ/IκBα/NF-κB] and [TOR/(S6K1, 4E-BP1)] in the respective tissues; (4) the results of this study indicate that Zn lactate exhibited superior efficacy compared to Zn sulfate in augmenting the immune response of head kidney, spleen and skin, as assessed through various health parameters. The aforementioned findings suggest that the inclusion of dietary Zn has a positive impact on the immune function of head kidney, spleen and skin. Using the acid phosphatase (ACP) levels observed in head kidney, spleen and skin, we have ascertained the optimal quantities of Zn in grass carp diets to be 70.59, 67.99 and 65.31 mg/kg, respectively.