Diabetic nephropathy (DN) is one dominating reason for death in diabetic patients, and its incidence is high. It has been reported that Yiqi Yangyin Tongluo prescription (YYTP) can relieve inflammation, and it owns better clinical effects in the treatment of DN. However, the molecular mechanisms of YYTP in the treatment of DN still keep unclear, and deeply investigations are needed. In this study, it firstly was manifested that YYTP can repress the lncRNA VIM-antisense 1 (VIM-AS1) expression in high glucose (HG)-evoked HK-2 cells. Overexpression of VIM-AS1 roll-backed the inhibitive impacts of YYTP on cell apoptosis in HG-triggered HK-2 cells. Additionally, it was uncovered that the attenuated autophagy of LC3B in HG-triggered HK-2 cells was counteracted after 20% YYTP treatment, but this phenomenon was further attenuated after VIM-AS1 amplification. Besides, VIM-AS1 can pull down FOXK2 protein, and overexpression of VIM-AS1 counteracted the suppressive effects of YYTP on forkhead box K2 (FOXK2)/mammalian target of rapamycin (mTOR) in HG-mediated HK-2 cells. In conclusion, it was firstly disclosed that YYTP targeted lncRNA VIM-AS1 to regulate FOXK2/mTOR to promote autophagy and inhibit cell apoptosis in DN progression. This discovery hinted that YYTP may be one valid drug for DN therapy.