Abstract: Objective To comprehend the effect of erythromycin on TREM-1, and investigate the mechanism on inflammation regulation of it. Methods U937 cells were cultured and separated into four groups: control group, LPS group, LPS+ TREM-1/FC fusion protein group and LPS+ erythromycin group. The cytokines, TNF-α, IL-6, IL-1β and sTREM-1, were measured by ELISA. The expression of membrane receptor and gene of TREM-1 were measured by flow cytometry and RT-PCR respectively. Results The top point of membrane expression of TREM-1 was （0.65±0.05）and （0.72±0.04）in TREM-1/FC fusion protein group and erythromycin group respectively, which was lower than that in LPS group（0.98±0.12）（P<0.01）. They couldn’t inhibit the expression of the gene, compared with LPS. The secretion of these cytokines was inhibited by them obviously, under LPS stimulation. The depressant effect of TREM-1/FC fusion protein was stronger than that of erythromycin, on sTREM-1 (P<0.01) and IL-6 (P<0.05), but the result was contrasted on TNF-α, IL-1β(P<0.05). Conclusions Erythromycin could inhibit the expression of TREM-1, which would depress the inflammatory reaction, and has the analogous clinical anti-inflammatory effect as TREM-1/FC fusion protein.