Election officials on Friday said early results indicated that 73-86% of the electorate had voted for Guelleh, with ballots from 149 voting booths counted.
Voters cast their ballots at more than 200 booths across the arid Red Sea state.
Earlier during the day, police in Djibouti fired teargas at hundreds of demonstrators protesting against the presidential election, in which Guelleh stood as the sole candidate after the opposition boycotted the poll.
Gathering outside the headquarters of the main opposition coalition, the Union of Democratic Alliance, protesters accused the government of suppressing democracy in the tiny but strategically important Horn of Africa country.
"We would rather die standing than follow on our knees," one banner read. Police moved quickly to disperse the rally, residents said. Police said no one had been hurt.
About 197,000 citizens of
700,000 were registered to vote
Closely related through the Somali Isa clan to Hasan Gouled Aptidon, Djibouti's founding president following independence from France in 1977, Guelleh became the country's second president after winning a 1999 election.
His sweeping victory then was widely regarded as fair by international observers.
But a parliamentary election in 2003, in which Guelleh's Union for Presidential Majority took every seat, was marred by criticism that voting was rigged.
"I regret having no opponent," Guelleh told Le Figaro newspaper in an interview published on Friday.
"I accuse the opposition of not having the courage to give voters the right to choose between several candidates," he was quoted as saying.
"I accuse the opposition of not having the courage to give voters the right to choose between several candidates"
Ismail Umar Guelleh,
About 197,000 of Djibouti's 700,000 people were registered to vote. The desert country is sandwiched between Eritrea and Somalia at the mouth of the Red Sea.
Guelleh campaigned hard for a second six-year term, focusing on development in a country that relies heavily on imports, transparency in local administration, and women's rights.
Since 2002, Djibouti has hosted US troops using the former French colony as a base to hunt down militants of the kind who in 1998 blew up US embassies in Kenya and Tanzania, killing more than 200 people.
A US State Department report this year criticised Djibouti for serious human rights abuses, noting that the government had limited the right of citizens to change their government.
Opposition was suppressed by control of the state media and unlawful arrests of critics, the report said.
Months after the election which catapulted Guelleh to power in 1999, his opponent in the presidential race, Musa Ahmad Idris, was arrested and jailed on charges of rebellion and acts of violence.
Idris had accused the government of rigging the poll.