Monitored rectal late morbidity using proctoscopy and a modified radiation therapy oncology group rectal bleeding scoring scale, in patients treated with permanent implant of I-125 and submitted to rectal protection with hyaluronic acid (HA) injecting in the perirectal fat to increase the distance between the prostate and the anterior rectal wall to decrease rectal toxicity. This is the first article looking at such injections in low-dose-rate brachytherapy patients and subsequent rectal toxicity. Between January 2005 and July 2006, a total of 69 consecutive outpatients with low- and intermediate-risk prostate cancer were enrolled in a clinical trial. First group received brachytherapy alone with I-125 and the second group received brachytherapy I-125 and protection of the rectal wall with HA. We injected 6-8cc of HA in the perirectal fat, to increase the distance between the prostate and the anterior rectal wall. Proctoscopic examinations with scoring of mucosal damage were performed according to a descriptive scale, described by Wachter et al. The median follow-up at time of endoscopy was 18 months. Toxicity measures included modified radiation therapy oncology group late bleeding toxicity grading. The hyaluronic and non-hyaluronic groups were similar for most patients, in tumor, treatment, and dosimetric characteristics. Patients treated with brachytherapy I-125 and rectal protection with HA had significantly smaller incidence of mucosal damage at the proctoscopic examinations (5% vs. 36%, p=0.002) and no macroscopic rectal bleeding (0% vs. 12%, p=0.047) than those treated with brachytherapy I-125 alone without HA. No toxicity was produced from the HA or its injection. The increased distance between the rectal wall and the prostate, as a result from the injection of HA in the perirectal fat, has significantly decreased the rectal dose from low-dose-rate brachytherapy. Patients treated with brachytherapy I-125 and protection rectal with HA had significantly smaller incidence of mucosal damage at the proctoscopic examinations and no macroscopic rectal bleeding than those treated with brachytherapy I-125 alone without HA.