Objective: To analyze the effects of twirling reinforcing and reducing manipulations on protein expres-sion in parietal cortex of spontaneously hypertensive rats (SHRs), and elucidate the main mechanisms and differences between two manipulations in hypertension treatment. Methods: Rats were randomly divided into the control, model, twirling reinforcing manipulation (TRFM), and twirling reducing manipulation (TRDM) groups. The control and model groups received catch and fixation stimulations once a day for 14 days. The TRFM and TRDM groups were intervened once a day for 20 min for 14 days. On days 0, 2, 6, 10, and 14 after acupuncture, rat systolic blood pressures (SBPs) were measured. Differential protein (DP) expression in the rat parietal cortices was detected. Thereafter, GO functional significance and KEGG pathway enrichment analyses were performed. Results: Compared with the model group, SBP of rats in the TRDM and TRFM groups decreased on days 6 and 10 of acupuncture, respectively (P=.009; P<.001). Moreover, SBP of the TRDM group was signif-icantly lower than that of the TRFM group on days 10 and 14 of acupuncture (P = .015; P = .013). Compared with control group, 601 and 1040 DPs were up-and downregulated, respectively, in the model group. Compared with model group, 44 and 28 up-and downregulated DPs were expressed, respectively, in the TRFM group. Compared with model group, expression of 616 and 427 up-and downregulated DPs, respectively, was found in the TRDM group. After combining the results of GO and KEGG enrichment analyses, five and one pathways were found to be related to the central antihypertensive mechanism of the parietal cortex during twirling reducing and reinforcing manipulations, respectively. Conclusion: TRDM showed a more effective antihypertensive effect on SHRs than TRFM; this antihy-pertensive effect was related to the regulation of different proteins and their biological functions.