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Aim: To investigate the effect of cholecystokinin octapeptide (CCK-8) on the diacylglycerol-protein kinase C (DAG-PKC) signaling pathway in rat pulmonary interstitial macrophages (PIM) stimulated by lipopolysaccaride (LPS). Methods:The PIM from rat lung tissues were isolated using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. DAG content and PKC activity were measured by radioenzymatic assay. The translocation of PKCξ was determined by semi-quantitative immunoblot analysis. Results:CCK-8, at high concentrations (1 × 10-6-1 × 10-5 mol/L), decreased DAG content and inhibited PKC activity and PKCξ translocation compared with that in rat resting PIM of a control group (P＜0.01). LPS increased DAG content, and promoted PKC activity and PKCξ translocation (P＜0.01). CCK-8 decreased LPS-induced DAG content and inhibited LPS-induced PKC activity and PKCξ translocation significantly at 1×10-8-1× 10-5 mol/L (P＜0.01). This inhibitory effect of CCK-8 could be abrogated partly by proglumide (non-selective CCK receptor antagonist),CR-1409 (selective CCK-A receptor antagonist), and CR-2945 (selective CCK-B receptor antagonist) in a concentration-dependent manner (P＜0.01). Conclusion:CCK-8 was a negative modulator of the DAG-PKC signaling pathway in rat resting PIM, which is very important for maintaining body homeostasis. It significantly inhibited LPS-induced DAG content, PKC activity and PKCξ translocation in a concentration-dependent manner. The CCK receptor, especially the CCK-A receptor, might play a major role in this process.