Abstract: 【Abstract】 Objective To explore the effect of Roxithromycin on expression of HDAC2 though HIF-1α in smoking asthma mice.Methods Forty female SPF BALB/c mice were divided randomly into 4 groups: control group (group C), asthma group (group A) ,smoking asthma group (group S) and Roxithromycin group(group R). To establish asthmatic and smoking asthma models with challenge of OVA and intervention with Roxithromycin. The different cells counts of bronchoalveolar fluid (BALF) were analysed. The change of pathematology in different groups were observed. The level of TNF-α in BALF was detected by Sand-wich ELISA.The level of HIF-1α and HDAC2 in lung homogenate were measured by Western blot. Results The ratios of eosinophil (EOS) neutrophile (Neu) 、lymphocyte（Lym）to the total cell numbers of BALF in group A and group S were significantly higher than that in group C (all P<0.01), while in group S the ratio of Neu was higher than that in group A (P<0.01). The ratio of EOS、Neu and Lym in group R were significantly decreased than those in group S (all P<0.01).Western blot showed the expression of HIF-1α in lung homogenate of group A（0.67±0.03）and group S(0.85±0.07) were higher than those in group C（0.42±0.03）.Meantime the expression of HIF-1α in group S was higher than that of group A , while the expression of HIF-1α in group R was lower than that of group S(all P<0.01).The expressions of HDAC2 in group A and group S were significantly decreased than those in group C (both P<0.01), while the HDAC2 level of group S was lower than that of group A and its level in group R was higher than that in group S (both P<0.05). There were significantly negative correlations between the expressions of HIF-1α and HDAC2 (r=－0.879，P<0.01)in lung .The level of TNF-α in BALF of group S was significantly higher than those of group A and group C,but it in group R was decreased than that in group S (all P<0.01). Conclusion Roxithromycin can decrease the airway inflammation of cigarette smoking asthma mice via increasing the expression of HDAC2 by down-regulating the expression of HIF-1α.