OBJECTIVE To evaluate the effect of Poria cocos (Schw.) Wolf hydroethanolic extract (PHE) against nephrotic syndrome (NS) in rats and to identify the potential active components from PHE. METHODS The high content compounds were isolated and purified by using column chromatography followed by preparative highperformance liquid chromatography (p-HPLC). Forty male Wistar rats with adriamycin (ADR)-induced NS were randomly divided into 5 groups, 8 in each group: model control group, positive control group (with prednisone treatment), PHE low-dose group, PHE middle-dose group and PHE high-dose group. Another 8 rats were recruited as vehicle control group. All rats received the intragastric administration of corresponding drugs or saline for 30 days. During the experimental period, rats' behavior and appearance were observed and recorded daily, and their body weights were recorded weekly. After treatment, 24-h urine samples were collected to evaluate the urine protein and urine creatinine (Ucr); then the rats were sacrificed to collect carotid blood and to determine the levels of serum total protein (TP), albumin (Alb), globulin (Glo), total cholesterol (TC) and cytokine interlukin-4 (IL-4). RESULTS Six acidic components were isolated and identified from the PHE section: pachymic acid, 15α-hydroxydehydrotumulosic acid, trametenolic acid, dehydropachymic acid, 3β-hydroxy-lanosta-7,9(11), 24-trien-21-oic-acid and dehydroeburicoic acid. Compared with the model control group, the urine protein content were significantly decreased in the PHE treatment groups and positive control group (P<0.05), especially PHE middle-dose group (P<0.01). The Ucr values and serum levels of TP, Glo, TC and IL-4 in PHE low- and middle-dose groups were also presented obvious recover tendency as compared with the model control group (P<0.05 or P<0.01). However, positive control group and all PHE groups indicated no significant therapeutic effect on raising Alb value, although PHE low- and middle-dose treatment groups showed better outcomes than positive control group (P>0.05). CONCLUSIONS PHE showed an encouraging therapeutic effect against ADR-induced NS in a rat model. PHE might be a group of effective substances for the treatment of NS.