Objective To investigate the effect of modified Dioscorea opposita Thunb. Pill on the protein expression of triggering receptor expressed on myeloid cells 2 (TREM2) and Iba1 and the number of Iba1-positive cells in the hippocampus of rats with Alzheimers disease (AD). Methods Sprague-Dawley rats were given intracerebroventricular injection of beta-amyloid (1-42) at both sides to establish a model of AD, and after the model was successfully established, the rats were divided into model group and traditional Chinese medicine (TCM) group, with 10 rats in each group. A total of 10 normal rats were selected as normal group for control. The rats in the normal group and the model group were given 10 mL/kg normal saline by gavage every day, and those in the TCM group were given 10 g/kg modified Dioscorea opposita Thunb. Pill by gavage every day. After 4 consecutive weeks of treatment by gavage, Western blot was used to measure the protein expression of TREM2 and Iba1 in the hippocampus, and immunofluorescent staining was used to measure the number of Iba1-positive cells. Results Compared with the normal group, the model group had a significant increase in the protein expression of TREM2 (P<0.05), and compared with the model group, the TCM group had a significant reduction in the protein expression of TREM2 (P<0.05). There was a significant increase in the protein expression of Iba1 (P<0.05). Compared with the model group, the TCM group had a significant increase in the number of Iba1-positive cells(P<0.05). Conclusion Modified Dioscorea opposita Thunb. Pill exerts a therapeutic effect on AD by influencing the protein expression of TREM2 and Iba1 and increasing the number of Iba1-positive cells in the hippocampus.