Dermal absorption of chlorpyrifos, an organophosphate insecticide is important because of its use in agriculture and control of household pests. The objectives of this study are to investigate fi rstly, the biochemical changes in the blood and secondly, histomorphometric changes in the hippocampus of adult mice following dermal application of chlorpyrifos in sub-toxic doses. Male Swiss albino mice (60 days) were segregated into one control and two treated groups (n=10). Chlorpyrifos, diluted with xylene, was applied in doses of 1/2 of LD₅₀ (E1) and 1/5 of LD₅₀ (E2) over the tail of mice of the two treated groups, 6 hours daily for 3 weeks. AChE levels in the serum and brain were estimated using a spectrophotometric method (Amplex Red reagent). Coronal serial sections were stained with 0.2% thionin in acetate buffer and pyramidal neurons of Cornu Ammonis of hippocampus were counted at 400× magnifi cation using Image Pro Express software. At the end of 3 weeks, body weights were reduced signifi cantly in E1 group. Serum AChE concentrations were reduced by 97% in E1 and 74% in E2 groups compared to controls. The neurons of CA 3 and CA 1 in the hippocampus showed evidences of morphological damage in both treated groups. Furthermore, the neuronal count was signifi cantly reduced in CA 3 layer of hippocampus in E1 group.