Objective To establish a cough variant asthma (CVA) guinea pig model induced by cigarette smoke exposure and OVA sensitization. Methods Twenty-four specific pathogen-free guinea pigs were randomLy assigned to three experimental groups: control (n= 8), OVA (n= 8), and CS ( cigarette smoke) +OVA ( n= 8). Guinea pigs in the OVA group were sensitized with ovalbumin (OVA)and those in the CS+OVA group were sensitized with ovalbumin and exposed to cigarette smoke. At the end of experiment, airway resistance (RI) challenged by four doses of methacholine (0. 2 mL, 0. 4 mL, 0. 6 mL, 0. 8 mg / mL) and lung compliance (Cydn) were measured to determine airway hyper-responsiveness (AHR), and cough latency and the frequency of coughing challenged by capsaicin within 10 minutes were analyzed to evaluate symptoms. Hematoxylin and eosin staining and the Ashcroft score were used to observe the state of lung injury. Results Compared with the control group, RI, Ashcroft score, and the frequency of coughing in OVA and OVA+CS groups were increased significantly, and Cydn and cough latency were decreased significantly. Compared with the OVA group, the OVA+CS group had better performance in terms of cough symptoms and RI, which was more similar to the characteristics of cough variant asthma. This may be closely related to appropriate reduction of the OVA dose. Conclusions The CS+OVA guinea pig model is more consistent with the clinical features of cough variant asthma and can be used as an animal model of cough variant asthma.