The 20-year-old Argentinian made only a minimal impact on the first team at Stamford Bridge after signing from Chilean side Audax Italiano in January 2008.
He will stay with Blackburn until January under the terms of the deal.
Rovers will then have first option on extending the deal providing Chelsea are willing to let him stay on loan for the remaining months of the season.
Di Santo could make his first appearance for Blackburn in Wednesday's home friendly against Hibernian.
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