OBJECTIVE: To study the relieving cough and eliminating phlegm effects of stemoninine combined with mogroside Ⅴ on mice, and select its optimal ratio. METHODS: 70 mice were selected in each experiment and randomly divided into 7 groups, namely solvent group (normal saline), codeine (15 mg/kg) or ambroxol (30 mg/kg) group (positive control), stemoninine group (30 mg/kg), mogroside Ⅴ group (30 mg/kg), stemoninine-mogroside Ⅴ combination group (30 mg/kg) with mass ratio of 2 ∶ 1, 1 ∶ 1, 1 ∶ 2, ig, once a day. Ammonia-induced cough experiment (positive drug was codeine) and tracheal phenol red excretion experiment (positive drug was ambroxol) were respectively conducted. Using cough latent period, cough times and volume of tracheal phenol red excretion as indexes, the antitussive and expectorant effects of drug in each group were compared. RESULTS: Compared with solvent group, cough latent period was obviously shortened, cough times was obviously reduced, volume of tracheal phenol red excretion was obviously increased in each administration group (P<0.05 or P<0.01). Compared with mogroside Ⅴ group, cough latent period was obviously shortened, cough times was obviously reduced in stemoninine-mogroside Ⅴ group with different mass ratios (P<0.05), and 2 ∶ 1, 1 ∶ 1 groups showed the best effects. Compared with stemoninine group, volume of tracheal phenol red excretion was obviously increased in stemoninine-mogroside Ⅴ group with different mass ratios (P<0.05), and 1 ∶ 1, 1 ∶ 2 groups showed the best effects. CONCLUSIONS: The combination of temoninine and mogroside Ⅴ shows synergistic effects on relieving cough and eliminating phlegm, stemoninine-mogroside Ⅴ mass ratio of 2 ∶ 1, 1 ∶ 1 can be used as preferred combination of reference.