Methomyl is a well-known insecticide that induces several side effects. Spirulina is a rich source of antioxidant and bioactive agents. The target of this experiment was to evaluate the possible ameliorative role of spirulina on some biochemical and histological alterations in rat livers caused by methomyl.  Forty adult albino rats were split into 4 groups, 10 rats for each, as follows: control group (GI):  rats of this group served as control rats, spirulina-treated group (GII): rats of this group received spirulina orally at a dose of 500 mg/kg b.wt daily for three weeks, methomyl-treated group (G III): rats of this group received methomyl orally at a dose level of 1/20 of LD₅₀ daily for three weeks and methomyl and spirulina-treated group (GIV): rats of this group orally received both methomyl and spirulina at the same doses in GII and G III for three weeks. After 24 hours from the end of the treatments, animals of all groups were sacrificed. Biochemical analyses were performed, including serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and albumin (ALB), total protein (TP), cholesterol (CHOL) and triglycerides (TG) levels. Additionally, liver tissues were used for the determination of malondialdehyde (MDA), interleukin-6 (IL-6), glutathione (GSH) levels, and catalase (CAT) activity. Liver tissues were also used for histological and immunohistochemical examinations. From the obtained results in the current study, it is concluded that spirulina antioxidant contents reduced methomyl-induced hepatotoxicity through biochemical, histological, and immunohistochemical observations.