Traditional first-line treatment of chronic bacterial prostatitis (CBP) is administration of empirical antibiotics. However, the efficacy rate is low and long-term antibiotic therapy can result in adverse events and bacterial resistance. For these reasons, a new treatment or preventive modality that can replace traditional antibiotic therapy is required. There are several reports that E. coli extract has a preventive effect on recurrent urinary tract infection (UTI). Cranberries are also known to have beneficial effects in preventing UTI. To evaluate the preventive effect of E. coli extract and cranberries on CBP, 48 rats were randomly divided into 4 groups; control, ciprofloxacin, E. coli extract, and cranberry groups. All drug treatments were conducted for 3 weeks, and then we developed a CBP rat model. After 4 weeks, the results of microbiological culture of prostate and urine samples as well as histological findings for the prostate were analyzed for each group. The infection rate in the ciprofloxacin group was significantly lower than that in the control group. The microbiological cultures of the prostate and urine samples demonstrated reduced bacterial growth in all experimental groups compared with the control group. Histopathologic examination showed significantly decreased prostatic inflammation in all groups compared with the control group. These results suggest that E. coli extract has a potential preventive effect on the development of CBP, and cranberry also exhibits promising activity in this context