Aim To investigate the effect of Na＋/H＋ exchanger-1 (NHE1) inhibitor amiloride on the degradation of apolipoprotein A1 (ApoA1)-induced ATP binding cassette transporter A1 (ABCA1) in the mice macrophages.Methods The peritoneal macrophages were collected from the mice at various indicated time points after intravenous injection of ApoA1. ABCA1 mRNA and protein levels in the macrophages were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Furthermore, the mice intervened with ApoA1 for 8 h were intraperitoneally injected with amiloride or calpain inhibitor ALLN. The treated mice were divided into four groups:control group, amiloride group, ALLN group and amiloride＋ALLN group. ABCA1 protein was detected by Western blot and calpain activity was assessed by fluorescence method in macrophages. Results After mice intervened with ApoA1, ABCA1 mRNA had no obvious change, but the level of ABCA1 protein increased rapidly, and reached the peak at 8 h, then gradually declined. The ABCA1 protein levels were higher in amiloride group, ALLN group and amiloride＋ALLN group than that in control group. The differences of ABCA1 protein level were not statistically significant in amiloride group, ALLN group and amiloride＋ALLN group at 0,4 and 8 h. Whereas the ABCA1 protein level in amiloride＋ALLN group was higher than those in amiloride group and ALLN group at 12 and 16 h. Compared with the control group, calpain activities were decreased in amiloride group, ALLN group and amiloride＋ALLN group. There were no obvious differences in calpain activity among amiloride group, ALLN group and amiloride＋ALLN group at each time point. Conclusions Amiloride inhibits the degradation of ApoA1-induced ABCA1 and calpain activity in mice peritoneal macrophages in vivo. It indicates that NHE1 may be involved in ABCA1 degradation at least in part by changing the activity of calpain.