This study was done to reveal the effect of antihistaminic drug (Diphenhydramine) on mouse uterus and its drainage lymph nodes after implantation of embryo. The non-pregnant mice were sacrificed at oestrus phase and the pregnant mice were randomly divided into two groups: (1) control group and (2) treated group with antihistaminic drug at a dose 0.52 mg ¼ ml/day. These animals were dosed daily from the day of vaginal plug till the sacrificed days 4.5, 6.5 post-coitus. The animals of each group were sacrificed then the uterus and its drainage lymph nodes were taken and stained with H&E and histochemical stains. At 4.5 day of pregnancy, the blastocyst was attached to the luminal epithelium, the stromal cells (fibroblasts) around the blastocyst were proliferated and differentiated into decidual cells, and a marked edema was observed in the endometrial stroma. Histochemical studies showed a decrease in the carbohydrate content of the mouse uterus, and an increase in the activities of alkaline and acid phosphatases compared to those of the normal mouse uterus at oestrus phase. At 6.5 day of pregnancy, the luminal epithelium around the blastocyst was completely destroyed, the uterine glands were disappeared from the decidual zone, and the decidualization of the stroma becomes more extensive forming the primary and secondary decidual zones. Histochemical investigations revealed an increase in the carbohydrate content and in the activities of both alkaline and acid phosphatases compared to those of the previous stage. Also, at this stage, there was a marked enlargement of the uterine drainage lymph nodes with the formation of secondary lymphatic follicles, containing germinal centers. In treated mice, the histological changes associated with implantation were inhibited. Histochemical studies showed a decrease in the carbohydrate content and in the activities of alkaline and acid phosphatases. Also, at 4.5, 6.5 days of pregnancy, there was a decrease in the size of the uterine drainage lymph nodes and their lymphatic follicles compared to those of the normal pregnant mice.