Tissue damage and its associated-inflammation act as tumour initiators or propagators. AMP-activated protein kinase (AMPK) is activated by environmental or nutritional stress factors, such as hypoxia, glucose deprivation, and other cell injury factors, to regulate cell energy balance and differentiation. We previously have reported that AMPK alpha 2 deficiency resulted in the energy deprivation in tumour-bearing liver and the enhanced-hepatocyte death. In this study, AMPK alpha 2 knockout mice and the liver metastasis model of colon cancer cells were used to address the role of AMPK alpha isoforms in tumour inflammation. First, we found that the AMPK alpha 2 deficiency exacerbated the liver injury and recruitment of macrophages. Meanwhile, although compensatory expression of AMPK alpha 1 was not significant after AMPK alpha 2 knockout, AMPK alpha 1 phosphorylation was elevated in remnant liver in AMPK alpha 2 knockout mice, which was positively associated with the enhanced energy deprivation in the AMPK alpha 2 deficient mice. Furthermore, the activated AMPK alpha 1 in macrophage contributed to its polarizing to tumour-associated phenotype. Thus, the enhanced tumour-associated inflammation and activation of AMPK alpha 1 in the AMPK alpha 2 deficient mice may exacerbate the tumour development by affecting the tumour inflammatory microenvironment. Our study suggests that the two isoforms of AMPK alpha, AMPK alpha 1 and AMPK alpha 2 play different roles in controlling tumour development.