Aim Effects of nitric oxide (NO),superoxide anion(O . 2 ) and polysaccharide krestin(PSK) on macrophage-mediated oxidation of LDL were investigated. Methods Mouse were given peritoneal injection PSK (control mouse were given injection physiological saline), peritoneal macrophages were collected and stimulated with low-density lipoprotein(LDL), γ-IFN, LPS and PMA. Contents change of nitrite, hydroperoxides and TBARS were measured. Results PSK-treated mouse peritoneal macrophages secreted much NO and produced less LOOH, TBARS than non-PSK-treated. Much NO and less LOOH, TBARS could be found to be produced by macrophage when stimulated with γ-IFN, LPS, macrophages stimulated with PMA appeared opposite effect. Conclusions The results indicated PSK has a protective effect, prevent cell from lipoperoxidative injury. γ-IFN and LPS could induce NO synthase activity and produce substantial NO. Stimulated macrophages were less efficient in oxidizing LDL. PMA can activate the respiratory burst, the stimulated cells were more effective than unstimulated cells in modifying LDL, and that O - 2 was of critical importance.