English fans threw bottles and cans at police and Milan supporters on the central Piazza del Duomo in front of the 14th century cathedral that dominates the square.
Verbal clashes broke out between four Milan fans and a group of around 200 Arsenal supporters, who threw cans and chased their Italian counterparts into the landmark Galleria Vittorio Emanuele II arcade adjoining the square.
The English fans were stopped by police but started throwing bottles.
One Arsenal fan suffered a head injury in the subsequent clashes while another was arrested before calm was restored.
The last 16, first leg match is due to kick off at 1945 GMT.
Milan have lost their last three home Champions League matches against English opposition, including a 2-0 reverse against the Gunners in 2008.
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