Abstract: In practice, mechanical equipments usually working with the variable speed and load, and the vibration signal of the equipments is nonlinear and nonstationary. The traditional fault diagnosis methods are prone to misdiagnosis or missed diagnosis. In order to solve the problem of feature extraction and intelligent diagnosis of mechanical fault vibration signal under variable working conditions, a fault diagnosis method combining optimized Variational Mode Decomposition (VMD) and Deep Transfer Learning(DTL) was proposed in this paper. First, Multiple Population Differential Evolution (MPDE) algorithm and envelope entropy fitness function were used to optimize VMD to solve the problem that the decomposition number k and penalty factor α were difficult to be determined adaptively. Second, the intrinsic mode functions of VMD decomposition were reconstructed according to the average kurtosis criterion. Continuous wavelet transform was used to process the reconstructed signal, and the time-frequency characteristics of the reconstructed signal were obtained. Third, combining the Residual Network (ResNet) with Transfer Learning (TL) model, the edge distribution adaptive method was used to reduce the difference between the source domain data set and the target domain data set of mechanical fault signal, and a deep transfer learning model for mechanical fault diagnosis under variable working conditions was constructed. Finally, the MPDE-VMD+DTL method was compared with the traditional BP neural network, ResNet convolution neural network and transfer component analysis (TCA) in different rolling bearing experimental datasets which contained CWRU, XJTU-SY, IMS and MCVN dataset. The results showed that the accuracy of fault diagnosis of MPDE-VMD+DTL method was 84.36%, and that of the BP neural network, ResNet and TCA were 23.60%, 71.63% and 19.68% respectively. MPDE-VMD+DTL method realized the end-to-end mechanical fault intelligent diagnosis under different working conditions, and had good generalization ability and robustness.