In the present study, we observed that the expression of AT1R and AT2R was significantly reduced in the bone tissues of osteoporotic mice after intestinal flora dysbiosis, and both losartan and PD123319 could alleviate osteoporosis, but the efficacy of PD123319 was significantly stronger than that of losartan (P = 0.0208), suggesting that the AT2R might be the main target. The gene discussed is AGTR1; the disease is osteoporosis.