Autophagy is catabolic machinery that regulates cellular homeostasis in normal and stress conditions. There is a contradiction concerning the role of autophagy in liver injury. It has been reported that autophagy may act as profibrogenic or anti-fibrogenic cellular machinery. Here we investigated the role of autophagy in high fat diet induced liver injury in mice. Mice were divided into four groups: normal diet feeding as control, high fat diet (HFD) feeding treated or not with chloroquine or rapamycin for autophagy modulation. The expression of active caspase 3, LC3 and P62 was evaluated in liver by western blot for testing the progressing of apoptosis and autophagy, respectively. Levels of mRNA of inflammation markers (Ccl2 and Ccl5) and fibrogenic markers (COL1a1 and PAI1) were quantified by QRT-PCR in liver of all animal groups, besides histological and biochemical means of general liver injury markers. The level of apoptosis, inflammation and fibrosis markers were increased in HFD mice and massively increased in chloroquine treated group whereas, rapamycin reduced all of them. Histopathological and biochemical observations coincided with the above mentioned results concerning liver injury under autophagy modulation. Autophagy acts as protective cellular machinery that attenuates the signs of liver injury including apoptosis, inflammation and fibrosis.