Objective To explore the expression of c-fos,bcl-2,bcl-xL gene and apoptosis in rats with diffuse brain injury combination secondary injury(SBI).Methods 40 rats were randomly divided into the normal control group 10,10 cerebral ischemia,head injury group 10 and group 10 SBI to immunohistochemical method to detect brain cells in the c-fos,bcl-2,bcl-xL expression and in-situ to apoptosis(TUNEL).Results The expression of brain injury group and SBI group of cortex area c-fos gene (23.6±9.4),(37.1±5.5)positive cells/entries/H was significantly higher than that of cerebral ischemia group (5.6±1.4) positive cells/entries/H(t= 3.458,t = 3.648, all P<0.01) ;the expression of brain injury group and SBI group cortex area bcl-2 gene (18.2±4.6) ,(15.6±3.7)positive cells/entries/H lower than that brain blood group(23.6±4.3)positive cells/entries/H(t=2.345, t=2.447 ,all P <0.05) ;the expression of bcl-xL gene changes llttle;the apoptosis SBI group cortex area (36.6±5.3)cells/0.1mm2 higher than the brain injury group (21.6±4.4) cells/0.lmm2 (t = 2.378 ,P < 0.05 );the apoptosis and level of bcl-2 expression showed a negative correlation(r = -0.857 ,P <0.01 ).Conclusion The expression of c-fos,bcl-2,bcl-xL were increased with closely related to apoptosis in rats with diffuse brain injury combination secondary injury.