Paraoxonase 1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). PON1 has the ability to inhibit lipid peroxides and to hydrolyze a wide variety of substrates such as esters, thioesters, phosphotriesterases, carbonates, lactones and thio lactones. We hypothesized that whether paraoxonase hydrolyses some carbazole P-lactam compounds or not. For this purpose, human serum paraoxonase (hPON1) was purified from human serum blood via two step procedure by using ammonium sulphate precipitation and sepharose-4B-L-tyrosinel-napthylamine-chromatograpy. The in vitro effects of P-lactam compounds on paraoxonase 1 (PON1) were investigated using paraoxon substrate. The results showed that carbazole P-lactam derivatives positively modulated paraoxonase enzyme activity. Among the compounds, 3g and 3h on PON enzyme were found to be the most powerful activators.