Circadian rhythm has been linked to cancer genesis and development, but the detailed mechanism by which circadian disruption accelerates tumor growth remains unclear. The purpose of this study was to investigate the effect of circadian disruption on tumor growth and metastasis in male C57BL/6 mice, using an experimental chronic jet lag model. Lewis lung carcinoma cells were inoculated into both flanks of the mice following 10 days of exposure to experimental chronic jet lag or control conditions. The effects on tumor growth and lung metastasis were assessed, and the effect on gene expression was detected using cDNA microarrays and real-time quantitative RT-PCR. Tumors grew faster in the experimental chronic jet lag mice compared to the control mice (P= 0.004). Lung metastases were found in 10 out of 24 mice in the chronic jet lag group, but only in 3 out of 24 mice in the LD group (P= 0.023). Microarray data showed that in both liver and tumors circadian disruption altered the expression of genes, including those related to the cell cycle, apoptosis, the immune response and metastasis suppressor genes. The expression of the Ndrg1 gene was suppressed by chronic jet lag. We conclude that circadian disruption can promote tumor progression and metastasis by affecting the expression of both tumor-related genes and metastasis suppressor genes.