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A highly selective and sensitive optical sensor was developed to colorimetric detect trace Fe3+ ions in aqueous solution. The sensor was the sulfasalazine (SSZ) functionalized microgels (SSZ-MGs), which were fabricated via in-situ quaternization reaction. The obtained SSZ-MGs had hydrodynamic radius of about 259 ± 24 nm with uniform size distribution at 25 °C. The SSZ-MG aqueous suspensions can selectively and sensitively response to Fe3+ ions in aqueous solution at 25 °C and pH of 5.6, which can be quantified by UV-visible spectroscopy and also easily distinguished by the naked eye. Job's plot indicated that the molar binding ratio of SSZ moiety in SSZ-MGs to Fe3+ was close to 1:1 with an apparent association constant of 1.72 × 104 M−1. A linear range of 0–12 μM with the detection limit of 0.110 μM (0.006 mg/L) was found. The obtained detection limit was much lower than the maximum allowance level of Fe3+ ions in drinking water (0.3 mg/L) regulated by the Environmental Protection Agency (EPA) of the United States. The existence of 19 other species of metal ions, namely, Ag+, Li+, Na+, K+, Ca2+, Ba2+, Cu2+, Ni2+, Mn2+, Pb2+, Zn2+, Cd2+, Co2+, Cr3+, Yb3+, La3+, Gd3+, Ce3+, and Bi3+, did not interfere with the detection of Fe3+ ions. [ABSTRACT FROM AUTHOR]