D-GLUCAN is a polysaccharide with multi-branching molecules derived from the cell wall of baker's yeast. It was reported to modulated innate immunity via interaction with membrane receptors on macrophages, neutrophils and natural killer cells and posses potent antioxidant and free radical scavenging capabilities. The aim of the present study was to investigate chemo-protective and radio-protective effect of D-glucan. Rats were orally (gavages) injected with D-glucan at dose of (20 mg/kg body wt) daily for three weeks. Mitomycin c (MMC) was administered three equal doses (1.5 mg/ kg) day after day for one week (2 nd week) before radiation exposure at 3 fractionated doses (2 Gy) day after day in the 2nd week. The investigation were carried out on the days 3 & 10 post radiation-exposure and MMC administration for the determination of bone marrow micronucleus (Mn) frequency and DNA fragmentation in blood lymphocytes. The results showed that the exposure of animals to MMC and/ or irradiation led to clearly defined DNA fragmentation. D-glucan administration resulted in a significant improvement in lymphocytes DNA fragmentation and amelioration of Mn frequencies at day 3 and more pronounced at day 10 post irradiation. This study indicates that D-glucan has radio and chemo-protective effects against oxidative stress as a result of γ-radiation and/ or MMC exposure. So, D-glucan may be used to reduce the genotoxicity effects of different anticancer drugs and to reduce their unwanted side effects.