Objective To investigate the effect of PKG on the secretion of IL-6, IL-10, and TNF-αin THP-1 macrophage-derived foam cells. Methods THP-1 monocytes were induced to construct macrophages by treating with 160 nmol/L TPA. Then the macrophages were further treated with 50 mg/L ox-LDL to become foam cells. Four groups were set in this study, including the macrophage group, the foam cell group, the group of foam cell treated with PKG agonist 8-Br-cGMP, and the group of foam cell treated with PKG inhibitor KT-5823. The morphology of THP-1 cells, macrophages and foam cells were observed under microscope. The cellular lipid accumulation was detected by oil red ostaining. The secretion of IL-6, IL-10, and TNF-α into the supernatant was detected by ELISA assay. Results The foam cell was obtained after macrophage incubated with ox-LDL for 48 hours. The secretion of IL-6 and TNF-α increased significantly from the foam cells than that from the macrophages (P<0.05). After the THP-1 monocyte-derived macrophages were incubated with 8-Br-cGMP, the secretion of IL-6 in the supernatant decreased significantly ( P < 0 . 05 ) and IL-10 level in the supernatant increased significantly (P < 0.05). After the macrophages were incubated with KT-5823, the secretion of IL-10 decreased significantly (P<0.05), but the secretion of IL-6 was not significantly changed (P>0.05). After incubation with 8-Br-cGMP, the secretion of IL-6 and TNF-α from the macrophage-derived foam cells decreased significantly (P < 0.05), but IL-10 increased significantly (P<0.05). After the foam cells were treated with KT-5823, the secretion of IL-6 and TNF-αwere also decreased significantly (P<0.05), with no significant change of IL-10 secretion (P > 0.05). Conclusions PKG may enhance the expression of anti-inflammatory cytokine IL-10, and inhibit the expression of inflammatory cytokine IL-6 and TNF-α, contributing to prevent the development of inflammation. PKG might have a potential anti-atherosclerosis effect.