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Introduction/Objective The aim of this paper was to verify the biocompatibility of the newly synthesized nanostructured material based on calcium aluminate after implantation into the subcutaneous tissue of rats. Methods The study included 18 rats aged 10–11 weeks, divided into two experimental groups (n = 9). In all animals, incision took place on the back and two pockets of 15 mm in depth were made, in which sterile polyethylene tubes with test materials [calcium aluminate cement (ALBO-CA), calcium silicate cement with the addition of hydroxyapatite (ALBO-CSHA), and mineral trioxide aggregate (MTA) for the control group) were implanted. Six rats of each group were sacrificed in three observational periods (seven, 15, 30 days). Pathohistological analysis included inflammation, bleeding, fibrous capsule, and tissue integrity around the implanted material. Results After seven days of treatment, ALBO-CA and ALBO-CSHA showed better tissue response compared to MTA, with a statistically significant difference in inflammation intensity (p = 0.2781). The difference in vascular congestion and thickness of the fibrous capsule after implantation of ALBO-CA material compared to MTA was also statistically significant (p = 0.5567). At the end of the 30-day evaluation period, an identical inflammatory response of connective tissue at the site of implanting ALBO-CA, ALBO-CSHA, and MTA (score of 0.7) was recorded. The formation of thick or moderately thick fibrous capsule was found to be the thickest in ALBO-CA (grade 3.7). There were no statistically significant differences between the parameters analyzed after 30 days. Conclusion Newly synthesized ALBO-CA showed a satisfactory tissue response and confirmed biocompatibility after implantation in subcutaneous tissue of rats. © 2018, Serbia Medical Society. All rights reserved.