The experiment conducted to reformulation of cimetidine antacid into Nano-liposome form for the reduction of worsening effect on the male reproductive system. Nano Liposome encapsulated cimetidine was formulated according to Bangham thin-film, in vivo challenge of ordinary and Nanoliopsome formulated form, the forty male mice distributed into 4 groups ten for each according to treatment Control mice: Negative control: Pro liposome dosed mice (Esome): Positive control empty liposome 1% 0.1mg/10g body weight daily orally Cimetidine dosed mice (CIM): 20mg/Kg body weight daily orally Liposome Cimetidine dosed mice (CIMsome): 20 mg/Kg body weight daily orally for 38 days. the liposome cimetidine standardization outcome was driven multi-lamellar;1-3, multi-vesicles type, size ranged 21.6-213.3 nm. The loading efficiency and entrapment percentage of cimetidine liposome 76.13 ± 6.91% and 80.06 ± 5.76 % respectively. The results of body condition of in cimetidine liposome treated group did not affect significantly the animals performances. Hormonal level of cimetidine liposome dosed group produce improvement. The endpoint of cimetidine liposome dosed group was recovered values and corrected modification in the morphometric indices (testicular weight to body weight ratio, testicular volume) and stereometric analysis of testicular tissue;(quantitation of spermatogenic cells and Leydig cells indices). The turbidimetric analysis that associated with a recovered in the sperm viability and lessening in sperm abnormalities in the cimetidine liposome dosed compared with ordinary cimetidine dosed group The antioxidant activity of liposome cimetidine clearly appear on the genetic material, reducing DNA abnormalities. The Liposome Cimetidine was partial protected the tissue of post testicular blood testes barrier from cimetidine direct effect.