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MacLoughlin is the form of the name most frequent in Connacht and Leinster, while McLaughlin is most common in Ulster, particularly in counties Antrim, Donegal and Derry. Both forms derive from the Irish and Scottish Mac Lochlainn, from the personal name Lochlann, from loch, "lake" or "fjord", and lann, meaning "land". It was a Gaelic name used for Scandinavia, and was applied to the Viking settlers of the early middle ages, becoming a popular name in its own right. The surname containing it has at least four origins in Ireland.

In Connacht there were at least two families of the name, minor branches of the O’Connors and the MacDermotts.

In the Inishowen peninsula of Co. Donegal, the family were among the northern Uí Néill , reputed descendants of the semi-mythical Niall of the Nine Hostages, who was reputed to be responsible for bringing St. Patrick to Ireland. They were the most powerful family of Cenél Eoghain, the tribal grouping claiming descent from Eogan, son of Niall, supplying 11 kings of that grouping and two High Kings between 1061 and 1241, when they were defeated by the leader of their rivals in the Cenél Eoghain, Brian Ó Néill and their place as effective rulers of Ulster taken by the O’Neills. Although the family fade almost completely from history after that defeat, the 19th century antiquarian John O’Donovan visited the reputed grave of Eogan, the progenitor of the Cenél Eoghain, in Iskaheen in the Inishowen peninsula in 1835 and reported meeting there "MacLoughlin, Chief of his name". MacLachlan and its variants is also common in Scotland; the Clan MacLachlan had their principla seat at Cowal in Argyll, and no doubt many McLaughlins in Ulster are of this stock.

In Co. Meath, the descendants of the tenth-century high king, Maolseachlann (or Malachy II), of the southern Uí Néill were first known as O'Melaghlin, later corrupted to MacLoughlin. By the 18th century O'Melaghlin had all but disappeared as a separate form.

.Alf Mac Lochlain (1924 - ) was formerly Director of the National Library of Ireland, but is best known now for his humourous, semi-surreal fiction.

John MacLoughlin (1784-1857) was well known for his role in the history of the Hudson Bay company.

Pedro Macloclin (1791-1845) became well known in Chile for his work in astronomy. His father, an emigrant from Leitrim, had become a successful merchant in Santiago.

McLoughlin households by county in the Primary Valuation property survey of 1848-64.
Click on a county name for a parish breakdown(paying).
Antrim 180
Armagh 52
Belfast city 41
Carlow 1
Cavan 40
Cork 3
Cork city 2
Derry 415
Donegal 740
Down 63
Dublin 51
Dublin city 31
Fermanagh 48
Galway 92
Kerry 10
Kildare 22
Kilkenny 4
Laois 33
Leitrim 206
Limerick 3
Limerick city 1
Longford 47
Louth 37
Mayo 225
Meath 41
Monaghan 14
Offaly 35
Roscommon 153
Sligo 158
Tipperary 24
Tyrone 253
Waterford 8
Westmeath 76
Wexford 16
Wicklow 8