BACKGROUND Interdigestive migrating motor complexes (MMC) produce periodic contractions in the gastrointestinal tract, but the exact mechanism of action still remains unclear. Intramuscular interstitial cells of Cajal (ICC-IM) participate in gastrointestinal hormone and neuromodulation, but the correlation between ICC-IM and MMC is also unclear. We found that xiangbinfang granules (XBF) mediated the phase III contraction of MMC. Here, the effects of XBF on gastric antrum motility in W/W-v mice and the effects of ICC-IM on gastric antrum MMC are reported. AIM To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility. METHODS The density of c-kit-positive ICC myenteric plexus (ICC-MP) and ICC-IM in the antral muscularis of W/W-v and wild-type (WT) mice was examined by confocal microscopy. The effects of XBF on gastric antrum slow waves in W/W-v and WT mice were recorded by intracellular amplification recording. Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/W-v and WT mice. RESULTS In the gastric antrum of W/W-v mice, c-kit immunoreactivity was significantly reduced, and no ICC-IM network was observed. Spontaneous rhythmic slow waves also appeared in the antrum of W/W-v mice, but the amplitude of the antrum slow wave decreased significantly in W/W-v mice (22.62 +/- 2.23 mV vs 2.92 +/- 0.52 mV, P < 0.0001). MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/W-v mice. The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/W-v mice (frequency, 3.53 +/- 0.18 cpm vs 1.28 +/- 0.12 cpm; amplitude index, 23014.26 +/- 1798.65 mV center dot 20 min vs 3782.16 +/- 407.13 mV center dot 20 min; P < 0.0001). XBF depolarized smooth muscle cells of the gastric antrum in WT and W/W-v mice in a dose-dependent manner. Similarly, the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg (P < 0.05). Atropine (0.1 mg/kg) blocked the enhancement of XBF in WT and W/W-v mice completely, while tetrodotoxin (0.05 mg/kg) partially inhibited the enhancement by XBF. CONCLUSION ICC-IM participates in the regulation of gastric antrum MMC in mice. XBF induces MMC III-like contractions that enhance gastric antrum motility via ICC-IM in mice.