The role of Syzygium cumini against chronic complications of Diabetes mellitus (DM), such as fungal infection and inflammation, has been poorly explored. Here, we evaluated the treatment with S. cumini aqueous seed extract (ASc, 100mg/Kg) and polymeric nanoparticles containing ASc (NPASc, 100mg/Kg) in diabetic rats infected or not by Candida albicans (CA). Male Wistar rats were divided in: control; DM; CA; CA+ASc; CA+NPASc; DM+CA; DM+CA+ASc; and DM+CA+NPASc. Rats were daily treated for 21 days, when glycemic profile, ectonucleotidase (NTPDase and 5'-NT), adenosine deaminase (ADA), acetylcholinesterase (AChE) and dipeptidyl peptidase IV (DPP-IV) activities and nitric oxide (NO) and cytokine levels were analyzed in serum, platelets, lymphocytes and tissues. The results showed that NTPDase, 5'-NT and ADA activities and NO, IL-1, IL-6, TNF-α and IFN-ɣ levels were increased in C. albicans, DM and DM+CA. The treatment with ASc and NPASc decreased ectonucleotidase and AChE activities and NO levels. Both treatments also prevented the increase in ADA activity and pro-inflammatory cytokines in cells and serum. In liver and pancreas, NPASc decreased NO levels more efficiently than ASc. The modulation of ectoenzyme activities can be one of the mechanisms by which S. cumini act on cytokines that affect the development of chronic complications in DM.