Police declared a gathering outside San Diego’s convention centre unlawful and made 35 arrests, as stones and water bottles were thrown.
Donald Trump was in San Diego, near the Mexican border, to hold a rally ahead of the June 7 California primary.
The Republican has pledged to build a border wall to keep out illegal immigrants.
The skirmishes flared as the convention centre emptied following Donald Trump’s rally, and supporters and opponents met in the streets, jeering and heckling each other.
Dozens of riot police officers had been deployed to separate them.
Some protesters scaled a wall of the centre to throw water bottles at police.
After ordering the crowds to disperse, riot police then moved them away from the city’s Gaslamp Quarter.
San Diego’s population is about one-third Latino and hundreds of thousands of people cross the border with Mexico legally each day.
The San Diego Police Department said that 35 arrests had been made and there was no damage to property and no injuries reported.
Donald Trump tweeted to the police after the event: “Fantastic job on handling the thugs who tried to disrupt our very peaceful and well attended rally.”
The New York billionaire is running unopposed in California after his Republican rivals pulled out and he reached the number of delegates needed to secure the nomination. It has yet to be formalized.
On May 27, Donald Trump backed out of an offer to debate with Democratic candidate Bernie Sanders, saying in a statement: “As much as I want to debate Bernie Sanders – and it would be an easy payday – I will wait to debate the first place finisher in the Democratic Party, probably Crooked Hillary Clinton, or whoever it may be.”
Bernie Sanders told reporters on the campaign trail that he hoped Donald Trump would change his mind.
“Well Mr. Trump, what are you afraid of?” the Vermont senator said, calling the Republican nominee a “bully”.
Donald Trump said the Democratic nominating process was “rigged” – and that Hillary Clinton and Democratic National Committee Chairwoman Deborah Wasserman Schultz would not allow Bernie Sanders to win the nomination.
The latest opinion polls suggest Hillary Clinton leads Donald Trump by about four percentage points.
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