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Objectives Evaluate the local and systemic effects of aqueous extract of green coffee (GCE) in colorectal carcinogenesis (CRC) induced in rats. Methods Adult Wistar rats (n = 48) were divided into two groups (C and T, n = 24). Group T was induced to CRC with 1,2-dimethylhydrazine (55 mg/kg, subcutaneously, weekly) for 5 weeks, and during this period all animals received standard AIN93-M diet. From week 6 to 15, the animals were divided into 4 groups (n = 12): C (healthy control fed AIN93-M diet), T (CRC- induced, fed AIN93-M diet), CGC (healthy control, fed AIN93-M diet + GCE), TGC (CRC-induced, fed AIN93-M diet + GCE). At 10th week, the pre-neoplastic lesions were evaluated in 4 rats from each group. The remaining rats (n = 8) were feed their experimental diet until the 15th week. In the last week, 24 h-urine collection was performed for intestinal permeability analysis using lactulose (100 mg/kg) and mannitol (50 mg/kg) administration. Afterwards, blood samples were collected to the analyses of plasma cytokines (TNF-alpha, interleukins IL-6, 10 and 12) and total antioxidant capacity (TAC). Large intestine content was collected for pH and secretory immunoglobulin A (sIgA) analyses. The microscopic lesions were evaluated in the colorectal mucosa. Results TGC group had the highest aberrant crypt foci (ACF) count, 51% higher compared to the T group. Intestinal permeability was increased in the T group. There was no significant difference in the quantification of cytokines TNF-alpha, IL-6, 10 and 12. Both TGC and T showed high values of TAC. Intestinal pH was significantly higher in CGC group compared to TGC. There was no significant difference in the quantification of sIgA between groups. The reduction of malignant neoplastic changes was 42% and of benign changes was 66% and there was a reduction of 33.33% and 20% of hyperplasia and dysplasia, respectively, in TGC compared with T group. Conclusions GCE was beneficial for intestinal permeability and controlled the development of neoplasms in the colorectal mucosa, without interfering with systemic inflammation, reinforcing that GCE reduces the risk of developing the CRC. Funding Sources This study was financed by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPES (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo), Brazil.