Objective To explore the effect of Kaolin combined with propranolol on matrix metalloproteinase-9 (MMP-9) in lungs of paraquate (PQ) intoxicated mice and the mechanism of protection for lung injury. Methods Fifty-four ICR mice were randomly divided into three groups, 18 mice in each group: namely control group, PQ intoxicated group and treatment group. The PQ intoxicated model was replicated by intra-gastric administration (ig) of PQ 100 mg/kg; after intoxication, 48 g/kg Kaolin combined with 3.2 mg/kg propranolol intra-gastric administration was immediately given to the treatment group, while in the control group, the same volume of normal saline ig was applied. All the mice were sacrificed at 6, 12 and 24 hours after disposal, and the lung was harvested to test the protein expression level of MMP-9 by Western Blot, and the lung tissue pathological changes were observed.Results There was no statistical significance in the protein expression levels of MMP-9 among the control group, PQ intoxicated group and treatment group at 6 hours after disposal (grey value: 0.655±0.045, 0.656±0.045, 0.641±0.036). The protein expression levels of MMP-9 in PQ intoxicated group were increased significantly compared with those in the control group at 12 hours and 24 hours after disposal (12 hours: 0.824±0.039 vs. 0.634±0.038, 24 hours: 0.742±0.039 vs. 0.658±0.041, bothP < 0.05), while the levels of treatment group were significantly lower than those in the intoxicated group (12 hours: 0.760±0.050 vs. 0.824±0.039, 24 hours: 0.686±0.041 vs. 0.742±0.039, bothP < 0.05). In PQ intoxicated group, early capillary dilation and congestion in lung tissue, a large number of inflammatory cells infiltration with mainly neutrophils in alveolar cavity and a small number of red blood cells exudation were seen at 12 hours; at 24 hours, capillary dilation at alveolar walls, congestion, swelling of endothelial cells, small flakes or large patches of inflammatory cell infiltration with mainly neutrophils in lungs were found. In the treatment group, the lung inflammatory cells infiltration, alveolar capillary dilatation, congestion, swelling of the endothelial cells, etc were also visible, but the degree of severity was significantly milder than those in the intoxicated group.Conclusion The interference of Kaolin combined with propranolol can significantly decrease the protein expression level of MMP-9 in lung tissue of acute paraquat poisoned mice that is possibly one of the mechanisms for prevention and treatment of lung injury in paraquat poisoning.