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Background: Urinary tract infection (UTI) is one of the most common bacterial diseases in children. This infection can lead to serious complications, such as chronic kidney injury, chronic renal failure, and even hypertension. The aim of this study was to investigate changes in serum levels of interleukin-8 in upper and lower urinary tract infections, and to investigate its association with the type of urinary tract involvement. Methods: This was a cross-sectional and prospective study. The study population consisted of all children aged 3 months to 12 years' old who referred to Amiralmomenin Hospital in Semnan city. By convenience sampling, 57 children were enrolled and received either oral or injectable treatment. Interleukin-8 serum levels were measured before and 3 days after treatment, by ELISA method and using available kits. DMSA scan was performed one week after admission to assess the severity of kidney parenchymal involvement in order to determine and distinguish between lower and upper urinary tract infections. Results: Totally 57 subjects with mean age 21.2 ± 20.76 months were enrolled. Children aged more than 20 months were more likely to have upper urinary tract infection than the other group (P=0.005). In males, the prevalence of upper urinary tract infection was significantly lower (P = 0.049). Children with upper urinary tract infection had a higher interleukin-8 concentration (P=0.001) than the lower urinary tract infection. Conclusion: IL-8 had higher serum concentrations in upper urinary tract infections compared to lower urinary tract infections. As a result, this test can be used as a suitable substitute for DMSA scan, to predict the type of urinary tract infection. Keyword: Interleukin 8, Infections, Urinary tract, Renal failure. How to cite this article: Mazaheri M. [Changes in Serum Levels of Interleukin-8 in Upper and Lower Urinary Tract Infections in 3 months to 12 years' children in Semnan]. Med J Tabriz Uni Med Sciences Health Services. 2019 June-July; 41(2):89-96.