Aim To investigate the role and significance of voltage dependent K⁺ channel（K_V） and ERK1/2 signal pathway in the pathological process of hypoxia hypercapnia pulmonary vasoconstriction （HHPV） in rats. Methods We made the second pulmonary artery rings of SD rats in vitro, and divided the rings randomly into: control group, hypoxia hypercapnia group, hypoxia hypercapnia+DMSO incubation group（HD group）, hypoxia hypercapnia+4-aminopyridione（4-AP） incubation group（4-AP group）, hypoxia hypercapnia+U0126 incubation group（U0126 group）, hypoxia hypercapnia+4-AP+U0126 incubation group（4-AP+U0126 group）. Under acute hypoxia hypercapnia condition, we observed the effects of the three stages of HHPV incubated by 4-AP or the combined application of 4-AP and U0126. At the same time, the values of rings’ tension changes were recorded . Results Under the acute hypoxia hypercapnia condition,we observed a biphasic pulmonary artery contractile response The second pulmonary artery rings were incubated by 4-AP which phase Ⅱ persistent vasoconstriction were enhanced compared with the HD group（P<0.05） U0126 can significantly relieve the phase Ⅱ persistent vasoconstriction created by 4-AP（P<0.05）. Conclusion The blocker of voltage dependent K⁺ channel-4-AP enhanced HHPV, U0126 can significantly relieve the phase Ⅱ persistent vasoconstriction created by 4-AP, which pointed out that the ERK1/2 signal pathway’s participation may be one of the important mechanisms of K_V’s regulation to the process of HHPV in rats.