Single stranded DNA breaks induced by Zinc sulfate in mice has been studied in vivo using Alkaline Single Cell Gel Electrophoresis (Comet assay). Mice were administered orally with doses of 5.70, 8.55, 11.40, 14.25, 17.10 and 19.95 mg/kg body weight of zinc sulfate respectively. The samples of whole blood were collected at 24, 48, 72, 96 hr and first week post-treatment and the assay was carried out to determine single strand DNA breaks as represented by comet tail-lengths. Results indicated a significant DNA damage at all the doses after treatment with zinc sulfate when compared to controls showing a clear dose-dependent response (p < 0.05). A gradual decrease in the tail-lengths from 48 hr post-treatment onwards was observed indicating a time dependent decrease in the DNA damage. The study confirms that zinc sulfate causes significant DNA damage at the doses used as revealed by comet assay.