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.
Police swiftly arrived but, according to Italian news agency ANSA, the Arsenal fans started hurling cans of beer. One Arsenal fan was arrested.The second round, first leg match is due to kick off at 21:45 (SA time).
Milan have lost their last three home Champions League matches against English opposition, including a 2-0 reverse against the Gunners in 2008.