Abstract: The analgesic and antiphlogistic actions of Sinomenine have been reported in a pre- vious paper. The purpose of the present experiment is to study the mode of antiphlogistic action of Sinomenine. Intraperitoneal injection of Sinomenine (60 mg/kg) reduced the swelling of the ankle joint of the rat hind leg caused by the injection of egg-white. Sinomenine decreased the content of ascorbic acid of the adrenals of the intact rat, but in rats anaesthetized with pentobarbital (40 mg/kg) administration of the drug failed to produce the same effect. In adrenalectomized or hypophysectomized rats Sinomenine did not exert the antiphlogistic action. In adrenalectomized mice, the LD₅₀ of Sinomenine was lower than in the control group. It was found that Sinomenine caused no significant change of the histamine content of the abdominal skin in rats, whereas subcutaneous injection of Polymyxin B (5 mg/ kg) markedly reduced the histamine content, but it did not inhibit the "arthritis" induced by injection of egg-white. These results indicated that Sinomenine exerted its antiphlogistic action on the pitui- tary-adrenal activity through the central nervous system, probably the hypothalamus. On the other hand, it also indicate that the mode of antiphlogistic action of Sinomenine has no relation to the release of histamine from skin in rats.