Objective:To observe effects of wrist-ankle acupuncture (WAA) onβ-endorphin (EP), nitric oxide (NO) in uterus tissue and prostaglandin F2α (PGF2α), substance P (SP) in serum of rats with primary dysmenorrhea. Methods:A total of 45 non-pregnant Wistar rats were randomly divided into a control group, a model group and a WAA group, 15 rats in each group. Rats in the model group and the WAA group received continuous abdominal subcutaneous injection of Diethylstilbestrol to establish dysmenorrhea rat models. On the first day after modeling, rats in the WAA group began to receive acupuncture on Point Lower 1 and Point Lower 2, once a day for 10 d. The control group and the model group didn’t receive any treatment. Writhing latencies and frequencies were recorded.β-EP and NO in uterus tissue homogenates and PGF2α, SP in serum were detected. Results:In the model group,β-EP and NO levels were the lowest among the groups, the serum PGF2α level was the highest, and serum SP level was the lowest. These measurements showed significantly difference between the model group and the control group (P<0.05). PGF2α in the WAA group was lower than that in the model group;β-EP, NO and SP levels were higher than those in the model group, with inter-group statistically significant differences (P<0.05). Conclusion: WAA may achieve analgesic effect through decreasing PGF2α, increasingβ-EP, NO and SP to relieve uterine cramps, increase blood flow and promote functional improvement.