ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis has been used as a traditional remedy against diabetes in many countries and its glucose-lowering effects have been demonstrated in animal studies. The active compounds and their possible mode of action are still unknown although it has been suggested that diterpenes may be responsible for the anti-diabetic effect of Salvia officinalis. AIM OF THE STUDY: To investigate whether the reported anti-diabetic effects of Salvia officinalis are related to activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma and to identify the bioactive constituents. MATERIALS AND METHODS: From a dichloromethane extract of Salvia officinalis able to activate PPARgamma several major metabolites were isolated by chromatographic techniques. To assess bioactivity of the isolated metabolites a PPARgamma transactivation assay was used. RESULTS: Eight diterpenes were isolated and identified including a new abietane diterpene being the epirosmanol ester of 12-O-methyl carnosic acid and 20-hydroxyferruginol, which was isolated from Salvia officinalis for the first time, as well as viridiflorol, oleanolic acid, and alpha-linolenic acid. 12-O-methyl carnosic acid and alpha-linolenic acid were able to significantly activate PPARgamma whereas the remaining metabolites were either unable to activate PPARgamma or yielded insignificant activation. CONCLUSIONS: Selected metabolites from Salvia officinalis were able to activate PPARgamma and hence, the anti-diabetic activity of this plant could in part be mediated through this nuclear receptor.