Indoxacarb is commonly used to effectively control pests, cockroaches, termites, fleas, and houseflies. Although the toxicological profile of indoxacarb had already been well characterized, we examined the possible toxicological interaction with indoxacarb and endotoxin. Male Swiss albino mice aged 8-10 weeks were orally administered indoxacarb dissolved in groundnut oil at 4 mg/ kg/day and 2 mg/kg/day for 90 days. On day 91, five animals from each group were challenged with lipopolysaccharides (LPS) at 80 µg/mouse, administered intranasally. Indoxacarb at 4 mg/kg significantly decreased Total leukocyte count, lymphocytopenia, and neutrophilia. Both doses of indoxacarb combined with LPS resulted in significant lymphocytopenia. Indoxacarb did not produce DNA damage in comet assay, but when combined with LPS, it resulted in a significant increase in tail length, tail moment, and olive moment. The data indicate that indoxacarb at 4 mg/kg administered orally for 90 days induced immune-response change. Further, both doses of indoxacarb, when combined with LPS, accelerate immunotoxicity and endotoxin-induced DNA damage.